This document provides information on therapy for diabetes mellitus. It defines diabetes and describes its pathophysiology and complications. Risk factors and diagnostic tests are outlined. The goals of therapy are to control symptoms and prevent complications. Nonpharmacologic therapy involves diet, exercise and weight control. Pharmacologic options include insulin, oral hypoglycemics like sulfonylureas, biguanides, thiazolidinediones and others. Adverse effects of different drugs are also discussed.

1. Therapy for Diabetes
Mellitus
Dr Md Shamshir Alam, Ph.D
Associate Professor
MM College of Pharmacy,
MMDU, Mullana

2. Definition
• Diabetes mellitus (DM) is a group of metabolic
disorders characterized by hyperglycemia and
abnormalities in carbohydrate, fat, and protein
metabolism.
• It results from defects in insulin secretion,
insulin sensitivity, or both.
• Chronic microvascular, macrovascular, and
neuropathic complications may ensue.

3. Risk factors for Diabetes Mellitus
• Family history
• Cardiovascular disease
• Obesity
• History of impaired fasting glucose or impaired glucose
tolerance
• Hypertension
• Polycystic ovary syndrome (PCOS)
• Gestational diabetes
• Ethnic groups at high risk—Asian Americans, Native
Americans, Latinos, Blacks

4. Pathophysiology
• Type 1 DM accounts for 5% to 10% of all
diabetes cases. It generally develops in childhood
or early adulthood and results from immune
mediated destruction of pancreatic β-cells,
resulting in an absolute deficiency of insulin.
• Hyperglycemia occurs when 80% to 90% of β-
cells are destroyed.
• Type 2 DM accounts for as many as 90% of DM
cases and is usually characterized by the presence
of both insulin resistance and relative insulin
deficiency.

5. Pathophysiology
• Type 2 DM occurs when a diabetogenic
lifestyle (excessive calories, inadequate
exercise, and obesity) is superimposed upon a
susceptible genotype.
• Uncommon causes of diabetes (1% to 2% of
cases) include endocrine disorders (e.g.,
acromegaly), gestational diabetes mellitus, and
medications (e.g., glucocorticoids).

6. Complications
• Microvascular complications include
retinopathy, neuropathy, and nephropathy.
• Macrovascular complications include coronary
heart disease, stroke, and peripheral vascular
disease.

7. Clinical Presentation
• TYPE 1 DIABETES MELLITUS:
• Individuals with type 1 DM are often thin and are
prone to develop diabetic ketoacidosis.
• Between 20% and 40% of patients present with
diabetic ketoacidosis after several days of polyuria,
polydipsia (excessive thirst), polyphagia (increased
hunger), and weight loss.

8. • TYPE 2 DIABETES MELLITUS:
• Patients with type 2 DM are often asymptomatic.
• However, the presence of complications may indicate
that they have had DM for several years.
• Lethargy, polyuria, nocturia, and polydipsia can be
present on diagnosis; weight loss is less common.

9. • Fasting plasma glucose— ˃126 mg/dL.
• Random sugar >200 mg/dL.
• OGTT>200 mg/dL
• OGTT and IV glucose tolerance test no longer used
routinely.
Diagnostic tests

10. Desired Outcome
• The goals of therapy in DM are:
• To ameliorate symptoms of hyperglycemia,
• To reduce the onset and progression of
microvascular and macrovascular
complications,
• To reduce mortality, and improve quality of
life.

11. NONPHARMACOLOGIC THERAPY
• For individuals with type 1 DM, the focus is on
regulating insulin administration with a balanced diet
to achieve and maintain a healthy body weight.
• In addition, patients with type 2 DM often require
caloric restriction to promote weight loss.
• Aerobic exercise can improve insulin resistance and
glycemic control in most patients and may reduce
cardiovascular risk factors, and improve well-being.
• Exercise should be started slowly in previously
sedentary patients.

12. 
Optimise BG control

Improve blood lipids

Control blood pressure
Consistent carbohydrate intake
(< 130 g/day)
Protein intake
(0.8 g/kg/day recommended for
prevention of nephropathy)
Moderate weight loss
(5-10% weight loss)
Increase physical activity
(Moderate aerobic exercise with a
starting goal of 150 minutes/week)
Space meals
(Eat three meals and two
snacks a day, avoid
skipping meals)
Low fat and calorie
restricted diet
(Saturated fat should be limited
to <7% of calorie)
NONPHARMACOLOGIC THERAPY

13. PHARMACOLOGIC THERAPY
• Rapid-acting insulin:
• Insulin lispro , and insulin aspart (E.g. NovoRapid®) :
• They have rapid onset and short duration of action and
are administered subcutaneously.
• They are usually not used alone but, rather, along with
a longer‐acting insulin for proper glucose control.
• Short‐acting insulin:
• Regular insulin (E.g. Actrapid®HM) is a short acting,
soluble, crystalline zinc insulin. Regular insulin is
usually given subcutaneously (or intravenously in
emergencies).

14. • Intermediate‐acting insulin:
• Neutral protamine Hagedorn (NPH) insulin
(Humulin N®) is a suspension of crystalline
zinc insulin combined with a protamine ( also
called insulin isophane).
• NPH insulin should only be given
subcutaneously (never intravenously) and is
useful in treating all forms of diabetes except
diabetic ketoacidosis or emergency
hyperglycemia.

15. • Long‐acting insulin:
• Insulin glargine (Lantus® ):
• Like the other insulins, it must be given
subcutaneously.
• It is a “peakless” human insulin analog.
• Insulin combinations
• Various premixed combinations of human
insulins, such as 70‐percent NPH insulin plus
30‐percent regular insulin.

16. • Adverse reactions to insulin
• Hypoglycemia
• weight gain, lipodystrophy (less common with
human insulin), allergic reactions, and local
injection site reactions.
• Oral Antidiabetic Drugs: Sulphonylureas:
• Short-acting: Tolbutamide:
– Appropriate in renal dysfunction.
– Gliclazide (Diamicron®).
• Intermediate-acting:
– Glipizide (Minidiab®).

17.  Long-acting:
 Chlorpropamide (Diabinese®): 250 mg daily
with breakfast; Max: 500 mg (disulfiram
reactions).
Glibenclamide- glyburide: (Daonil®): 5 mg
daily with or immediately after breakfast; Max:
15 mg daily. Active metabolite → decrease dose
in renal dysfunction.
 Adverse effects:
Hypoglycaemia; increased appetite and weight
gain.
Nausea, vomiting, diarrhoea and constipation.
Hypersensitivity.

18. Biguanides
• Metformin (Glucophage®) is the only available
biguanide.
• Mechanism: May involve increased tissue
sensitivity to insulin and/or ↓ gluconeogenesis
• Metformin does not cause hypoglycemia or
weight gain.
• Recommended for obese or insulin resistant
diabetic patients
• Adverse effects:
– Decreased appetite; nausea, vomiting and
diarrhea; lactic acidosis (rarely); decreased
absorption of vitamin B12.

19. Alpha glucosidase inhibitor
• Acarbose (Glucobay®) : No hypoglycemia.
• Mechanism: Inhibits α-glucosidase in brush
borders of small intestine → ↓ formation of
absorbable carbohydrate → ↓ postprandial
glucose → ↓ demand for insulin.
• Adverse effects:
–Gastrointestinal discomfort, flatulence, soft
stools, diarrhoea.
–Recent concern over potential hepatotoxicity

20. Meglitinide analog
• Repaglinide and nateglinide:
• Mechanism of action: Like the sulfonylureas,
their action is dependent on functioning
pancreatic β cells.
• In contrast to the sulfonylureas, the
meglitinides have a rapid onset and a short
duration of action.
• They are categorized as postprandial glucose
regulators.

21. Thiazolidinediones
• Also known as Glitazones: Insulin sensitizers
• Rosiglitazone (Avandia®); Pioglitazone:
• Mechanism: Bind to nuclear peroxisome
proliferator-activating receptors (PPARS) involved
in transcription of insulin responsive genes →
sensitization of tissues to insulin plus ↓ hepatic
gluconeogenesis and triglycerides and ↑ insulin
receptor numbers.
• Adverse effects:
– Less hypoglycaemia than sulfonylureas.
– Weight gain; oedema; headache, anaemia.